Transgenic Overexpression of Myocilin Leads to Variable Ocular Anterior Segment and Retinal Alterations Associated with Extracellular Matrix Abnormalities in Adult Zebrafish.

Myocilin is an enigmatic glaucoma-associated glycoprotein whose biological role remains incompletely understood. To gain novel insight into its normal function, we used transposon-mediated transgenesis to generate the first zebrafish line stably overexpressing myocilin [Tg(actb1:myoc-2A-mCherry)]. qPCR showed an approximately four-fold increased myocilin expression in transgenic zebrafish embryos (144 hpf). Adult (13 months old) transgenic animals displayed variable and age-dependent ocular anterior segment alterations. Almost 60% of two-year-old male, but not female, transgenic zebrafish developed enlarged eyes with severe asymmetrical and variable abnormalities in the anterior segment, characterized by corneal limbus hypertrophy, and thickening of the cornea, iris, annular ligament and lens capsule. The most severe phenotype presented small or absent ocular anterior chamber and pupils, due to iris overgrowth along with dysplastic retinal growth and optic nerve hypertrophy. Immunohistochemistry revealed increased presence of myocilin in most altered ocular tissues of adult transgenic animals, as well as signs of retinal gliosis and expanded ganglion cells and nerve fibers. The preliminary results indicate that these cells contributed to retinal dysplasia. Visual impairment was demonstrated in all old male transgenic zebrafish. Transcriptomic analysis of the abnormal transgenic eyes identified disrupted expression of genes involved in lens, muscular and extracellular matrix activities, among other processes. In summary, the developed transgenic zebrafish provides a new tool to investigate this puzzling protein and provides evidence for the role of zebrafish myocilin in ocular anterior segment and retinal biology, through the influence of extracellular matrix organization and cellular proliferation.

Epidemiology and clinical presentation of feline presumed hereditary or breed-related ocular diseases in France: retrospective study of 129 cats.

OBJECTIVES: This study aimed to describe the epidemiology and clinical presentation of presumed hereditary or presumed breed-related ocular diseases in a population of cats in France. METHODS: Medical records from between September 2013 and August 2017 were reviewed to identify cats with at least one presumed hereditary or breed-related ocular disease. Cats with concurrent, or a history of, ocular or systemic infectious diseases were excluded. Signalment, history and clinical findings were recorded. RESULTS: Of the 1161 cats that presented to our institution during the study period, 129 were diagnosed with at least one presumed hereditary or presumed breed-related ocular disease (11.1%, 95% confidence interval [CI] 9.3-12.9). Five ocular abnormalities had a prevalence of >1%: entropion, corneal sequestration, persistent pupillary membrane, cataract and retinal dysplasia. The prevalence of entropion was 2.2% (95% CI 1.3-3.0), with Persians (P = 0.03), Maine Coons (P <0.01) and male cats (P <0.01) being over-represented. The prevalence of corneal sequestration was 2.4% (95% CI 1.5-3.3), with Persians (P <0.01) and Exotic Shorthairs (P = 0.02) being over-represented. Persistent pupillary membranes and cataracts had the same prevalence of 2.3% (95% CI 1.5-3.2), with no particular sex or breed significantly over-represented. Retinal dysplasia had a prevalence of 1.6% (95% CI 0.8-2.3) and Persian cats were over-represented (P = 0.04). Anterior segment dysgenesis had a low prevalence (0.9%, 95% CI 0.4-1.5), with all affected cats being domestic shorthairs and this breed therefore was over-represented (P = 0.04). CONCLUSIONS AND RELEVANCE: In a French population of cats, presumed hereditary or breed-related ocular diseases accounted for 11.1% of all ocular diseases. Cataracts, corneal sequestration, persistent pupillary membrane, entropion and retinal dysplasia were the most common conditions. Statistical breed over-representation was observed for entropion, corneal sequestration and retinal dysplasia. We recommend that more systematic screening of feline species is conducted.

A Splicing Mutation in Slc4a5 Results in Retinal Detachment and Retinal Pigment Epithelium Dysfunction.

Fluid and solute transporters of the retinal pigment epithelium (RPE) are core components of the outer blood-retinal barrier. Characterizing these transporters and their role in retinal homeostasis may provide insights into ocular function and disease. Here, we describe RPE defects in tvrm77 mice, which exhibit hypopigmented patches in the central retina. Mapping and nucleotide sequencing of tvrm77 mice revealed a disrupted 5' splice donor sequence in Slc4a5, a sodium bicarbonate cotransporter gene. Slc4a5 expression was reduced 19.7-fold in tvrm77 RPE relative to controls, and alternative splice variants were detected. SLC4A5 was localized to the Golgi apparatus of cultured human RPE cells and in apical and basal membranes. Fundus imaging, optical coherence tomography, microscopy, and electroretinography (ERG) of tvrm77 mice revealed retinal detachment, hypopigmented patches corresponding to neovascular lesions, and retinal folds. Detachment worsened and outer nuclear layer thickness decreased with age. ERG a- and b-wave response amplitudes were initially normal but declined in older mice. The direct current ERG fast oscillation and light peak were reduced in amplitude at all ages, whereas other RPE-associated responses were unaffected. These results link a new Slc4a5 mutation to subretinal fluid accumulation and altered light-evoked RPE electrophysiological responses, suggesting that SLC4A5 functions at the outer blood-retinal barrier.

Retinal structural and microvascular abnormalities in retinal dysplasia imaged by OCT and OCT angiography.

OBJECTIVE: To describe the in vivo structural characteristics of multifocal and geographic retinal dysplasia visualized with advanced retinal imaging including confocal scanning laser ophthalmoscopy (cSLO), optical coherence tomography (OCT), en face OCT, and the novel vascular imaging technique OCT angiography (OCTA). DOGS STUDIED AND PROCEDURES: Two dogs were diagnosed with unilateral multifocal or geographic retinal dysplasia and underwent advanced retinal imaging under general anesthesia at the Retinal Disease Studies Facility of the University of Pennsylvania. RESULTS: In both cases, the morphological pattern of the lesions was similar including outer retinal folds that invaginated and formed tubular retinal rosettes, surrounding a central inner retinal thickening (multifocal) or plaque (geographic). The two dogs had multiple vascular anomalies in the lesions such as increased tortuosity, abnormal change of vessel diameter including aneurysms and capillary network disruption. We also identified increased autofluorescence by AF cSLO with short wavelength light source (488 nm and barrier filter at 500 nm), and several areas of photoreceptor loss associated with the lesions. CONCLUSION: The use of OCTA allowed the identification of microvascular abnormalities associated with multifocal and geographic retinal dysplasia in two dogs. To our knowledge, this is the first report where the dye-free OCTA technique is used to study vascular lesions in canine retinas.

Unilateral Familial Exudative Vitreoretinopathy: Clinical Profile and Pathology.

We report a case of a newborn with unilateral retinal detachment that could not be repaired. At examination under anesthesia, the retina was markedly abnormal and a presumptive diagnosis of retinal dysplasia was made. Several years later, the eye was enucleated because it was blind and painful. Final pathology was consistent with familial exudative vitreoretinopathy (FEVR). The literature describing unilateral retinal dysplasia is sparse. This case adds to the clinical spectrum of pathologic findings in FEVR.

Retinal detachment secondary to vitreoretinopathy in two closely related warmblood horses.

BACKGROUND: To describe the clinical, diagnostic imaging, and histopathological findings of two visually impaired closely related horses and to identify a possible cause. CASE DESCRIPTION: Two warmblood horses, with a common dam and sire, were presented to the ophthalmology department of Liège for investigation of impaired vision. Information collected included physical and ophthalmic examination findings, results of ocular ultrasound, electroretinogram, magnetic resonance imaging (MRI), and histopathology. Ophthalmic examination, ocular ultrasound and MRI revealed a complete retinal detachment (RD) in the left eye and vitreous synaeresis in both eyes of both horses. Electroretinograms showed a normal response in both right eyes but a total loss of the retinal response in their left eyes. Histopathologic examination revealed multifocal retinal dysplasia in both left eyes. CONCLUSION: In these two horses, RD has likely been caused by the congenital posterior segment abnormalities of the vitreous and the retina. A vitreoretinopathy is highly suspected and is possibly hereditary in these closely related siblings.

In vivo imaging comparison of unilateral circular retinal plaques in retriever dogs to dysplasia and detachment in the English Springer Spaniel.

PURPOSE: To compare the scanning laser ophthalmoscopy (SLO), optical coherence tomography (OCT), and fluorescein angiography (FA) findings in retrievers with a single unilateral circular retinal plaque to those of an English springer spaniel with bilateral retinal dysplasia. PROCEDURES: A retrospective record review identified three dogs with circular retinal plaques that underwent SLO and OCT; in two of the three dogs, FA was also completed. Morphologic changes, lesion measurements, and angiogram characteristics were documented. An English springer spaniel with bilateral retinal dysplasia that had undergone SLO, OCT, and FA was used for comparison. RESULTS: Scanning laser ophthalmoscopy of the retriever dogs revealed circular retinal plaques with a dark periphery located in the tapetal retina. OCT revealed a thickening of the nerve fiber layer corresponding to the circular pattern observed on SLO. Within the circular plaque, the retina was predominantly of normal architecture. FA revealed variable hypofluorescence of both the rim and the center of the circular lesion throughout the early angiogram phases. In the late recirculation phase, small multifocal areas of hyperfluorescence were observed. OCT of geographic retinal dysplasia in the English springer spaniel revealed disorganization of both inner and outer retinal layers, and retinal detachment. CONCLUSIONS: Circular plaques observed in the tapetal retina are predominantly formed by a thickening of inner retina, while retinal dysplasia has disorganization of both inner and outer retinal layers. Further etiologic research is needed, including pedigree mapping to determine whether retinal plaques are an acquired or inherited condition.

Etiology of Retinal and Cerebellar Pathology in Western Pacific Amyotrophic Lateral Sclerosis and Parkinsonism-Dementia Complex.

PURPOSE: To reexamine the etiology of a unique retinal pathology (linear and vermiform sub-retinal tubular structures) described among subjects with and without neurodegenerative disease in former high-incidence foci of Western Pacific amyotrophic lateral sclerosis and parkinsonism-dementia complex (ALS/PDC) in Guam (USA) and the Kii peninsula of Honshu island (Japan). METHODS: Analysis of published and unpublished reports of 1) ALS/PDC and the retinal and cerebellar pathology associated therewith and 2) exogenous neurotoxic factors associated with ALS/PDC and the developing retina and cerebellum. RESULTS: ALS/PDC retinal and cerebellar pathology matches persistent retinal and cerebellar dysplasia found in laboratory animals given single in utero or postnatal systemic treatment with cycasin, the principal neurotoxic component in the seed of cycad plants traditionally used for food (Guam) or oral medicine (Kii-Japan), both of which have been linked to the human neurodegenerative disease. CONCLUSION: ALS/PDC-associated retinal and cerebellar dysplasia could arise from in utero exposure to methylazoxymethanol, the genotoxic metabolite of cycasin that results from maternal ingestion of this azoxyglucoside. These results support the environmental toxic etiology of retinal and brain pathology in ALS/PDC.

Ophthalmic manifestations of congenital protein C deficiency: a case report and mini review.

BACKGROUND: Homozygous protein C (PC) deficiency is a potentially fatal disease with ocular blinding presentation or sequela. CASE PRESENTATION: A 5 month-old boy was presented for evaluation of leukocoria. He had a history of frequent bruises and PC deficiency, treated with warfarin. His intraocular pressure was normal. In the left eye leukoma with anterior segment dysgenesis, shallow anterior chamber, and cataract were observed. Fundus was not visible. B-scan revealed a closed funnel retinal detachment. His right eye had a normal anterior segment and a thin retina with anomalous retinal vascular branching at equator and peripheral retina. A fibrovascular tuft on the optic nerve head with induced traction on superior arcade was visible. Total loss of a and b wave of both were appreciated in electroretinography (ERG). Fluorescein angiography (FA) showed very severe leakage at the junction of the vascularized and non-vascularized retina and optic nerve head. Favorable outcome was achieved with lasering of avascular retina in the right eye. CONCLUSION: The potential for protein C deficiency should be assessed in all infants with leukocoria, anterior segment dysgenesis, retinal detachment and retinal dysplasia. Early diagnosis could save the child's life and vision.

Oculo-skeletal dysplasia in five Labrador Retrievers.

OBJECTIVE: To describe the clinical features and diagnostic findings of Labrador Retrievers with oculo-skeletal dysplasia (OSD). ANIMAL STUDIED: Five privately owned dogs. PROCEDURES: Medical records of dogs diagnosed with OSD from 2008 through 2018 were reviewed. Patients were excluded if lacking disease confirmation through genetic testing (Optigen RD/OSD). Information collected included signalment, physical and ophthalmic examination findings, results of ocular ultrasound and electroretinogram, and digital radiographs of forelimbs and pelvis. RESULTS: All five dogs were Labrador Retrievers, confirmed to be homozygote for the OSD mutation. The main physical abnormalities were vision deficits (5 dogs), short-limbed dwarfism (5), carpal valgus (4), and color dilution alopecia (4). The main ophthalmic anomalies were cataracts (10 eyes), vitreous syneresis (10), retinal separation (6), persistent hyperplastic primary vitreous (2), lens coloboma (2), microphakia (2), and persistent tunica vasculosa lentis (1). Ocular ultrasound and electroretinogram confirmed the diagnoses of retinal separations and persistent hyperplastic primary vitreous. Radiographic changes included shortening of ulna and curved radius (5 dogs), elbow incongruity and osteoarthritis (4 dogs), hip dysplasia (3), and coxofemoral osteoarthritis (2). Available follow-up information (2 dogs) showed progression of cataract from incipient to mature in one dog, necessitating cataract surgery, and progression of cataract and lameness in another dog. CONCLUSIONS: The clinical findings of OSD are described in five Labrador Retrievers. DNA testing is critical to diagnose OSD and help eradicate this condition from the breed. Progression of cataracts and osteoarthritis in dogs with OSD warrants yearly monitoring.

Focal/multifocal and geographic retinal dysplasia in the dog-In vivo retinal microanatomy analyses.

PURPOSE: To examine the in vivo microanatomy of retinal folds and geographic lesions in dogs with acquired or inherited retinal dysplasia. MATERIAL AND METHODS: Thirteen dogs had retinal microanatomy evaluation under general anesthesia using cSLO/sdOCT; two eyes had noninherited multifocal retinal folds, five had inherited multifocal retinal folds (drd1 or drd2), and 10 geographic retinal dysplasia. Retinas from two drd2 carrier dogs were examined by histology and immunohistochemistry (IHC) after in vivo imaging. RESULTS: Retinal folds are the common feature of acquired focal/multifocal or geographic retinal dysplasia, are indistinguishable structurally from those associated with syndromic oculoskeletal dysplasia, and represent outer nuclear layer invaginations and rosettes visible by sdOCT. In dogs heterozygous for oculoskeletal dysplasia, the folds form clusters in a perivascular distribution along superior central vessels. IHC confirmed photoreceptor identity in the retinal folds. The geographic dysplasia plaques are not focally detached, but have inner retinal disorganization and intense autofluorescence in cSLO autofluorescence mode that is mainly limited to the geographic lesion, but is not uniform and in some extends beyond the plaques. CONCLUSION: We propose that the autofluorescent characteristic of the geographic lesions is associated with an inner retinal disruption associated with perivascular or infiltrating macrophages and phagocytosis of cellular debris. As well, we suggest restructuring the examination forms to distinguish the folds that are sporadically distributed from those that have a perivascular distribution as the latter likely represent carriers for drd. In this latter group, DNA testing would be a helpful tool to provide specific breeding advice.

A SIX6 Nonsense Variant in Golden Retrievers with Congenital Eye Malformations.

Causative genetic variants for more than 30 heritable eye disorders in dogs have been reported. For other clinically described eye disorders, the genetic cause is still unclear. We investigated four Golden Retriever litters segregating for highly variable congenital eye malformations. Several affected puppies had unilateral or bilateral retina dysplasia and/or optic nerve hypoplasia. The four litters shared the same father or grandfather suggesting a heritable condition with an autosomal dominant mode of inheritance. The genome of one affected dog was sequenced and compared to 601 control genomes. A heterozygous private nonsense variant, c.487C>T, was found in the SIX6 gene. This variant is predicted to truncate about a third of the open reading frame, p.(Gln163*). We genotyped all available family members and 464 unrelated Golden Retrievers. All three available cases were heterozygous. Five additional close relatives including the common sire were also heterozygous, but did not show any obvious eye phenotypes. The variant was absent from the 464 unrelated Golden Retrievers and 17 non-affected siblings of the cases. The SIX6 protein is a homeobox transcription factor with a known role in eye development. In humans and other species, SIX6 loss of function variants were reported to cause congenital eye malformations. This strongly suggests that the c.487C>T variant detected contributed to the observed eye malformations. We hypothesize that the residual amount of functional SIX6 protein likely to be expressed in heterozygous dogs is sufficient to explain the observed incomplete penetrance and the varying severity of the eye defects in the affected dogs.

Novel ocular findings in oculodentodigital dysplasia (ODDD): a case report and literature review.

BACKGROUND: Oculodentodigitaldysplasia (ODDD; MIM no. 164200) is a rare hereditary disorder caused by mutations in the gene GJA1.Ocular disorders included microcornea, cornea opacity and glaucoma. However, few studies described fundus findings. MATERIALS AND METHODS: Ophthalmic examination included visual acuity measurement, intraocular pressure (IOP) measurements, slit-lamp biomicroscopy, B-scan ultrasonography, Ultrasound biomicroscopy (UBM), spectral-domain optical coherence tomography (SD-OCT), ERG and retcam fluorescein angiogram. In addition, blood samples were taken from this patient for mutation analyze of GJA1. RESULT: The ophthalmic features of this patient were microcornea, cornea opacity, glaucoma as expected. Interestingly, the patient had a normal axial length with refractive status of emmetropia, but extremely retinal dysplasia and severe choroid thinning was noted. Flash electroretinogram (ERG) was extinguished in both eyes. This study identified a novel mutation c.91A>T in the GJA1 gene associated with fundus abnormalities. Bioinformatics and structural modeling suggested the mutation to be pathogenic. CONCLUSION: Our research expanded not only the mutation spectrum, but also the clinical characteristics of ODDD. To the best of our knowledge, this is the first report on anatomical and functional chorioretinal changes in ODDD patients. These novel ocular features highlight the importance of fundus morphological and functional evaluation in ODDD. ABBREVIATIONS: ODDD: oculodentodigital dysplasia; OCT: optical coherence tomography; ERG: electroretinogram; TACT: teller acuity card test; UBM: ultrasound biomicroscopy; MW: molecular weights; AL: axial length; Cx43: connexin 43; RPE: retinal pigment epithelium; RGCs: retinal ganglion cells; FEVR: familial exudative vitreoretinopathy; ROP: retinopathy of prematurity.

Persistent hyperplastic primary vitreous in two piglets.

Two Large Yorkshire piglets were diagnosed as persistent hyperplastic primary vitreous (PHPV). In case 1, the white cord-like structure extending from optic disc to lens was observed in the normal-sized right eye. Case 2 showed buphthalmos of the right eye. The internal structure of the right eye was unclear due to bleeding, but a white cord-like structure was slightly observed. In both cases, histological examinations revealed the fibrovascular cord-like structure in hyaloid vitreous. The retina was detached, and dysplastic nervous tissue was observed in anterior vitreous. Immunohistochemistry using various neural markers suggested that dysplastic nervous tissue was derived from the detached neural retina. By the characteristic macroscopic and histopathological features, both cases were diagnosed as PHPV. To our knowledge, this is the first report of swine PHPV.

Genome-wide linkage and haplotype sharing analysis implicates the MCDR3 locus as a candidate region for a developmental macular disorder in association with digit abnormalities.

BACKGROUND: Developmental macular disorders are a heterogeneous group of rare retinal conditions that can cause significant visual impairment from childhood. Among these disorders, autosomal dominant North Carolina macular dystrophy (NCMD) has been mapped to 6q16 (MCDR1) with recent support for a non-coding disease mechanism of PRDM13. A second locus on 5p15-5p13 (MCDR3) has been implicated in a similar phenotype, but the disease-causing mechanism still remains unknown. METHODS: Two families affected by a dominant developmental macular disorder that closely resembles NCMD in association with digit abnormalities were included in the study. Family members with available DNA were genotyped using the Affymetrix GeneChip Human Mapping 250K Sty array. A parametric multipoint linkage analysis assuming a fully penetrant dominant model was performed using MERLIN. Haplotype sharing analysis was carried out using the non-parametric Homozygosity Haplotype method. Whole-exome sequencing was conducted on selected affected individuals. RESULTS: Linkage analysis excluded MCDR1 from the candidate regions (LOD < -2). There was suggestive linkage (LOD = 2.7) at two loci, including 9p24.1 and 5p15.32 that overlapped with MCDR3. The haplotype sharing analysis in one of the families revealed a 5 cM shared IBD segment at 5p15.32 (p value = 0.004). Whole-exome sequencing did not provide conclusive evidence for disease-causing alleles. CONCLUSIONS: These findings do not exclude that this phenotype may be allelic with NCMD MCDR3 at 5p15 and leave the possibility of a non-coding disease mechanism, in keeping with recent findings on 6q16. Further studies, including whole-genome sequencing, may help elucidate the underlying genetic cause of this phenotype and shed light on macular development and function.

Lachrymal Gland Basal Cell Adenocarcinoma in a Ferret (Mustela putorius furo).

A 1 cm diameter mass was detected in the caudal superotemporal area of the left eye of a 6-year-old neutered male ferret (Mustela putorius furo). The mass and the left eye were removed surgically. Microscopical examination revealed a tumour of the adnexal gland of the eye that had invaded the surrounding ocular muscle. The tumour was composed of basal-type epithelial cells arranged in a solid, or occasionally tubular, pattern. Immunohistochemically, the tumour cells expressed cytokeratin and p63, but not smooth muscle actin. Based on these findings, the tumour was diagnosed as a basal cell adenocarcinoma of the lachrymal gland. In addition to the tumour, the retina of the left eye was detached and folded at the centre of the globe. This is the first report of a non-human case of basal cell adenocarcinoma of the lachrymal gland.

Blindness in a wild American black bear cub (Ursus americanus).

An approximately six-month-old wild American black bear (Ursus americanus) was found wandering in Saskatchewan and was presented to the Veterinary Medical Centre of the Western College of Veterinary Medicine for apparent blindness. Clinical examination confirmed an inability to navigate a photopic maze, bilateral tapetal hyper-reflectivity, fundi devoid of retinal vessels, and small pale optic nerve papillae. Single-flash electroretinography revealed A and B-wave amplitudes of approximately 40 and 140 microvolts, respectively, in both eyes. Histologic abnormalities included bilateral optic papillary mineralization and bilateral segmental optic nerve degeneration, with occasional intralesional lymphocytes confirmed with immunohistochemistry for CD3+. There was also bilateral multifocal retinal dysplasia, gliosis, lymphocytic retinitis, a complete lack of retinal blood vessels, an intravitreal vascular membrane, and a mild lymphocytic-plasmacytic uveitis with small pre-iridal cellular membranes. The presence of a positive ERG in a blind bear with numerous retinal ganglion cells and degenerative changes in the optic nerve are most consistent with vision loss due to optic nerve injury, which given the young age of the bear likely occurred during ocular development. The presence of ocular inflammation suggests this injury resulted from an inflammatory/infectious process. The etiology could not be determined. Hepatic concentrations of vitamin A were within the normal reference range for domestic species. Pan-herpesvirus PCR and immunohistochemistry for canine distemper virus and Toxoplasma gondii were negative, although this does not rule out these or other infectious etiologies. This represents the first case report of neonatal or congenital ocular abnormalities in an ursid species.

Leber Congenital Amaurosis: Genotypes and Retinal Structure Phenotypes.

Leber congenital amaurosis (LCA) patients of 10 known genotypes (n = 24; age range, 3-25 years) were studied clinically and by optical coherence tomography (OCT). Comparisons were made between OCT results across the horizontal meridian (central 60(o)) of the patients. Three patterns were identified. First, there were LCA genotypes with unusual and readily identifiable patterns, such as near normal outer nuclear layer (ONL) across the central retina or severely dysplastic retina. Second, there were genotypes with well-formed foveal architecture but only residual central islands of normal or reduced ONL thickness. Third, some genotypes showed central ONL losses or dysmorphology suggesting early macular disease or foveal maldevelopment. Objective in vivo morphological features could complement other phenotypic characteristics and help guide genetic testing of LCA patients or at least permit a differential diagnosis of genotypes to be made in the clinic.

Retinal dysplasia in American pit bull terriers--phenotypic characterization and breeding study.

OBJECTIVE: The purpose of this study was to investigate the inheritance and phenotype of retinal dysplasia (RD) in the American pit bull terrier. ANIMALS STUDIED: A breeding colony established from a single female pure-bred American pit bull terrier dog with RD. PROCEDURES: A female pure-bred American pit bull terrier with RD was donated to the Veterinary Hospital of Federal University of Paraná, Curitiba, Brazil. A breeding colony was established and the phenotype and inheritance of the condition investigated. Regular ophthalmic examinations and fundus photography were performed on three generations of offspring from the founder animal. Some animals were additionally studied by optical coherence tomography. Ocular histopathology was performed on some animals from the colony. RESULTS: Fifty-seven offspring were produced in two generations from the affected founder female. Thirty-two were diagnosed with RD and showed a spectrum of severity of lesions including multifocal, and or geographic lesions and some developed retinal detachment. Histologic examination demonstrated retinal folds, rosettes, and areas of retinal detachment. The affected dogs were shorter in stature than the unaffected littermates. Breeding studies suggested the trait has an autosomal dominant mode of inheritance. DNA testing showed that the affected dogs were negative for the known gene mutations for canine dwarfism with RD. CONCLUSION: This is a report of a novel inherited form of RD that affects American pit bull terriers.